2024 Catalysts: Positive Clinical Data, Two
Planned NDAs, Company Launch of Hope Therapeutics; FDA QIDP award
in cUTI and New Schizophrenia Opportunity
- Executed Term Sheet from an institutional investor for an
initial $7.5 million note, subject to
common closing requirements, primarily to replace current debt,
clearing the path to a Hope Therapeutics share distribution, with
provision for funding up to $30
million to fund pipeline opportunities
- Positive data from a Phase 2b/3
trial of NRX-101 in Treatment Resistant Bipolar Depression (TRBD);
trial demonstrated depression efficacy comparable to standard of
care and significant reduction of akathisia (P=0.025). Akathisia is
a potentially lethal side effect of all serotonin-targeted
antidepressants and is associated with suicide. The study
additionally demonstrated a 30% advantage in sustained remission
from suicidality that was not statistically-significant at this
sample size
- Above findings of reduced suicidality mirror the results of the
Company's prior STABIL-B trial in acutely suicidal patients and
also mirror the results of an independent published trial
- Company plans to file a New Drug Application (NDA) for
Accelerated Approval under Breakthrough Therapy and Priority Review
of NRX-101 in treatment of bipolar depression in people at risk of
akathisia, based on the Phase 2b/3
and STABIL-B data
- Company has developed patentable pH neutral formulation for
ketamine that will be suitable for both intravenous and
subcutaneous administration. Ketamine efficacy data are in hand
from 4 clinical trials. Three manufacturing lots are now initiated
(required for NDA) and Company plans to initiate the NDA by
July
- HOPE Therapeutics (which focuses on care delivery, not drug
development) has partnered with representatives of ketamine clinic
providers nationwide to construct a care platform that will include
ketamine, operational support, and digital therapeutic extensions.
In advance of FDA approval, HOPE is actively in the sales process
to supply ketamine under 503b
pharmacy licensure to meet the national ketamine shortage declared
by FDA. HOPE is planned to be spun out as a separate company to be
owned by NRx, current NRx shareholders, and new investors; Term
Sheets received from prospective anchor investors for $60 million of new investment, once publicly
listed
- Data expected shortly in 200-person DOD-funded trial of
D-cycloserine (DCS), the key component of NRX-101, to treat chronic
pain, conducted by Northwestern
University. Statistical analysis plan and data unlock have
been approved by Northwestern IRB
- NRX-101 in the treatment of Complicated Urinary Tract Infection
(cUTI) granted Qualified Infectious Disease Product (QIDP), Fast
Track, and Priority Review designations. Company has now
demonstrated that NRX-101 does not damage the microbiome of the
gut, in contrast to all other advanced antibiotics and is less
likely to cause C. Difficile infection (a potentially lethal
side effect of antibiotic treatment). NRx is reviewing partnership
options
- Executed Memorandum of Understanding with Fondation FundaMental
for rights to develop potential disease modifying drug for
Schizophrenia. If successful, this would represent the first drug
to reverse the underlying disease mechanism of schizophrenia,
rather than simply treating symptoms.
- Management to host a conference call, May 14, 2024, at 4:30 PM
ET
RADNOR,
Pa., May 14, 2024 /PRNewswire/ -- NRx
Pharmaceuticals, Inc. (Nasdaq: NRXP) ("NRx Pharmaceuticals", the
"Company"), a clinical-stage biopharmaceutical company, today
announced its financial results for the quarter ended March 31, 2024, and provided a business
update.
"NRx has had an incredibly productive start to 2024, delivering
positive data from our phase 2b/3
trial of NRX-101 in suicidal bipolar depression, where we
demonstrated what could potentially be a best-in-class medication
for people with bipolar disorder. To our knowledge, this is the
first successful clinical trial ever conducted with an oral
antidepressant in patients with suicidal depression who have been
excluded from all antidepressant trials in the past. We plan to
file a New Drug Application based on these and previous findings.
In addition, we have advanced Hope Therapeutics and IV Ketamine,
HTX-100, towards the filing of an NDA this summer, and continue to
prepare to capitalize on the opportunity for NRX-101 in chronic
pain and complicated UTI," said Stephen
Willard, J.D., Chief Executive Officer and Director of NRx
Pharmaceuticals. "Together these opportunities constitute
treatments that can meet considerable unmet medical need in up to
75,000,000 patients across the country. Obviously, this would build
incredible value for our shareholders. We are dedicated to
bringing hope to life and I thank our team and shareholders for
their ongoing hard work and support. Lastly, we are pleased to have
signed a term-sheet to replace the toxic debt on our balance sheet
with a new commitment from a solid, institutional investor."
First Quarter Clinical, Regulatory and Corporate
Highlights
Development of NRX-101 for Suicidal Treatment-Resistant Suicidal
Bipolar Depression
The Company announced final data from the recently completed
phase 2b/3 trial of NRX-101 in
suicidal bipolar depression, with a significantly improved safety
profile as demonstrated by a statistically significant reduction in
akathisia, an adverse event considered by many experts to be a
precursor to suicide. Given the vital need for safer medications in
this at-risk population, we plan to submit an NDA to the US FDA for
treatment of bipolar depression patients at risk of akathisia,
based on these data as well as additional data from our
STABIL-B1 trial.
|
Efficacy Measures:
Repeated Measures Mixed Model LS Mean
Differences
|
|
|
Through Day
28
|
Through Day
42
|
|
|
LOCF
No
|
LOCF
yes
|
LOCF
No
|
LOCF
Yes
|
|
MADRS Depression
Score
|
LS Mean
Δ
|
p-value
|
LS Mean
Δ
|
p-value
|
LS Mean
Δ
|
p-value
|
LS Mean
Δ
|
p-value
|
|
-4.0
|
0.09
|
-7.7
|
0.03
|
-3.7
|
0.04
|
-7.7
|
0.04
|
|
Suicidality Rating
Scale C-SSRS
|
LS Mean
Δ
|
p-value
|
LS Mean
Δ
|
p-value
|
LS Mean
Δ
|
p-value
|
LS Mean
Δ
|
p-value
|
|
-0.5
|
NS
|
-1.3
|
0.04
|
-0.6
|
NS
|
-1.5
|
0.02
|
|
Clinical Global
Impression CGI-SS
|
LS Mean
Δ
|
p-value
|
LS Mean
Δ
|
p-value
|
LS Mean
Δ
|
p-value
|
LS Mean
Δ
|
p-value
|
|
-0.4
|
NS
|
-2.9
|
0.05
|
-0.6
|
NS
|
-2.9
|
0.02
|
|
During 2024, the Company began working in unison with Alvogen
and Lotus Pharmaceuticals to plan the final development and
commercialization of NRX-101. These partners recently advanced
$5 million of the first milestone to
the Company. Final licensing of the product, expected in Q2 2024,
will yield a total of $9 million in
milestone payments together with assumption of future development
costs by our partners. The partnership provides for potential
milestones of $329 million and a
royalty reaching 15% on Net Sales.
NRX-101 for Treatment of Chronic Pain:
In 2023, the Company licensed US Patent 8,653,120 for the
use of DCS in chronic pain and filed a now-accepted Investigational
New Drug (IND) application with the FDA to initiate commercial drug
development of NRX-101 in chronic pain. Data lock has now
been achieved in a 200-person randomized prospective trial funded
by the US DOD (NCT 03535688) in which patients with chronic pain
were randomly assigned to DCS 400mg/day vs. placebo. Should
these results support efficacy of DCS in the treatment of chronic
low back pain, they are expected to provide a Breakthrough Therapy
path towards treatment of chronic pain with DCS and DCS-containing
medicines.
Incorporation of HOPE Therapeutics and progress towards an NDA
for HTX-100 (IV ketamine) in the treatment of suicidal
depression
Intravenous ketamine has now become a standard of care for acute
treatment of suicidal depression, in the absence of an FDA-labeled
product. Intranasal Esketamine is approved by the FDA (SPRAVATO®),
but has not demonstrated a benefit on suicidality and is not
approved for use in patients with bipolar depression. Attempts to
use intranasal racemic ketamine for suicidal depression have
failed.
The Company has formed data-sharing partnerships to license
clinical trial data from a French Government-funded trial and two
NIH-funded trials all of which demonstrate efficacy of racemic
Intravenous ketamine against depression and two of which
demonstrate statistically significant benefit vs suicidality. The
Company's role is to reformat these data into the required
presentation required for review by the FDA.
In contrast to nasal ketamine, Intravenous racemic ketamine
demonstrates dramatic and immediate reduction of suicidality in
patients with both Major Depressive Disorder and Bipolar
Depression. Grunebaum and colleagues demonstrated a rapid and
statistically significant reduction in Suicidal Ideation (SSI) at
day 1 (p=0.0003) and in depression (P=0.0234), as measured by the
Profile of Mood States (POMS) among patients randomized to IV
Ketamine compared to those randomized to midazolam. This trial
was published in the American Journal of Psychiatry Grunebaum,
et.al.2. Abbar and colleagues similarly published 84%
remission from suicidality on the Columbia Suicide Severity Rating
Scale (C-SSRS) in patients treated with ketamine, vs. 28% in those
treated with placebo (P<.0001). This trial was published in the
British Medical Journal3. Data are expected to be
transmitted to FDA by July 2024.
In November 2023, the Company
initiated manufacture of ketamine together with Nephron
Pharmaceuticals, Inc. (West Columbia,
SC) to develop a single patient presentation of ketamine.
Nine months of real-time stability is ongoing, the minimum
stability time required for a New Drug Application.
A long-term challenge with ketamine is that the current
formulation (KETALAR®) is highly acidic. While it is suitable for
intravenous use, it cannot be administered subcutaneously. In
March 2024 the Company demonstrated
the formulation of a pH neutral patentable form of IV ketamine that
it anticipates will have widespread applicability both in treatment
of depression and chronic pain.
Treatment of Urinary Tract Infection (UTI) and Urosepsis:
Although treatment of UTI is quite different from use of NRX-101
to treat Central Nervous System disorders, D-cycloserine was
originally developed as an antibiotic because of its role in
disrupting the cell wall of certain pathogens. During Q3
2023, NRx tested NRX-101 and its components against resistant
pathogens that appear on the Congressionally mandated Qualified
Infectious Disease Product (QIDP) list and proved in vitro
effectiveness against antibiotic-resistant E. coli, Pseudomonas,
and Acinetobacter. Accordingly, NRx was granted QIDP
designation, Fast Track Designation, and Priority Review by the US
FDA in January 2024.
In recent years, increased antibiotic resistance to common
pathogens that cause urinary tract infections and urosepsis (i.e.,
sepsis originating in the urinary tract) has resulted in a marked
increase in cUTI, hospitalization, and death from urosepsis. The US
Center for Disease Control and Prevention reports that more than
1.7 million Americans contract sepsis each year, of whom at
least 350,000 die during their hospitalization or are
discharged to hospice (CDC Sepsis Ref.)4. There
are approximately 3 million patients per year who contract cUTI in
the US annually (Lodise, et. al.)5. Additionally, should
NRX-101 succeed in clinical trials, the Company will consider
developing a follow-on product that is anticipated to achieve
another 20 years of patent exclusivity.
A key challenge in the treatment of cUTI is the tendency of
advanced antibiotics to cause C. Difficile infection, which is
fatal in 10% of those who contract it over the age of 65 and
results in prolonged hospitalization in many more. The Company
recently announced data demonstrating that NRX-101 does not
compromise the intestinal microbiome, unlike common antibiotics
including Clindamycin and Ciprofloxacin. Should these findings be
documented in human patients, NRX-101 would represent the only
treatment for cUTI that does not cause C. Difficile infection.
In The Company does not anticipate funding this initiative with
core NRx assets and is exploring structures for partnership
opportunities. Should the Company or its partners succeed in
serving 10% of the cUTI market, the Company believes that the
revenue from NRX-101 has the potential to hundreds of million
annually, based on 3 million cases per year in the US and potential
pricing of over $3,500/course of
therapy.
Financial Results for the Quarter and Year Ended December 31, 2023
For the three months ended March 31,
2024, NRx Pharmaceuticals reduced net loss from $11.0 million in the first quarter of 2023 to
$6.5 million in 2024, representing a
41% improvement year over year. For that same period, Research and
Development expenses decreased from $3.7
million in 2023 to $1.7
million in 2024, as clinical trial enrollment concluded. The
$2.0 million decrease is related
primarily to a decrease of $1.6
million in clinical trial expenses, $0.2 million in regulatory and process
development costs, and $0.1 million
in stock-based compensation. The Company also recorded a 26%
reduction in general and administrative expenses during the
quarter, from $5.8 million in 2023 to
$4.3 million in 2024. The decrease of
$1.5 million is related primarily to
a decrease of $1.2 million in
insurance expenses, $0.4 million
employee expense, and slightly offset by other general and
administrative expenses.
As of March 31, 2024, the Company
had $1.3 million in cash and cash
equivalents, not including the $5.1
million of working capital committed by Alvogen. This
included a reduction of corporate indebtedness to Streeterville LLC
of $2.2 million. Subsequent to
March 31, 2024, we increased working
capital by $3.3 million from equity
sales. Over the first three months of 2024 the Company improved
access to working capital by $8
million in total, representing $2.9
million from equity sales and $5.1
million from the Alvogen milestone advance, while reducing
corporate indebtedness by 50%.
NRx continues to implement operational efficiencies to extend
cash runway and maintain focus on our path to generating revenue
and value for our shareholders.
Please see detailed financials on our Form 10-Q, filed with the
SEC and available on our website.
Conference Call and Webcast Details
A live webcast of the conference call will be available on the
Company's website at 4:30 p.m. ET
today, at https://ir.nrxpharma.com/events. An archive of the
webcast will be available on the Company's website for 30
days. Participants that are unable to join the webcast can
access the conference call via telephone by dialing domestically
1-800-717-1738 or internationally 1-646-307-1865.
About NRx Pharmaceuticals
NRx Pharmaceuticals is a clinical-stage biopharmaceutical
company developing therapeutics based on its NMDA platform for the
treatment of central nervous system disorders, specifically
suicidal bipolar depression, chronic pain and PTSD. The Company is
developing NRX-101, an FDA-designated investigational Breakthrough
Therapy for suicidal treatment-resistant bipolar depression and
chronic pain. NRx has partnered with Alvogen and Lotus around the
development and marketing of NRX-101 for the treatment of suicidal
bipolar depression. NRX-101 additionally has potential to act as a
non-opioid treatment for chronic pain, as well as a treatment for
complicated UTI.
NRx has recently announced plans to submit a New Drug
Application for HTX-100 (IV ketamine), through Hope Therapeutics,
in the treatment of suicidal depression, based on results of
well-controlled clinical trials conducted under the auspices of the
US National Institutes of Health and newly obtained data from
French health authorities, licensed under a data sharing agreement.
NRx was awarded Fast Track Designation for development of ketamine
(NRX-100) by the US FDA as part of a protocol to treat patients
with acute suicidality.
About HOPE Therapeutics, Inc.
HOPE Therapeutics, Inc.
(www.hopetherapeutics.com) is a Specialty Pharmaceutical
Company, wholly-owned by NRX Pharmaceuticals focused on development
and marketing of an FDA-approved form of intravenous ketamine for
the treatment of acute suicidality and depression together with a
digital therapeutic-enabled platform designed to augment and
preserve the clinical benefit of NMDA-targeted drug therapy.
Notice Regarding Forward-Looking Statements
The
information contained herein includes forward-looking statements
within the meaning of Section 21E of the Securities Exchange Act of
1934, as amended, and Section 27A of the Securities Act of 1933, as
amended. These statements include, among others, statements
regarding the proposed public offering and the timing and the use
of the proceeds from the offering. Forward-looking statements
generally include statements that are predictive in nature and
depend upon or refer to future events or conditions, and include
words such as "may," "will," "should," "would," "expect," "plan,"
"believe," "intend," "look forward," and other similar expressions
among others. These statements relate to future events or to the
Company's future financial performance, and involve known and
unknown risks, uncertainties and other factors that may cause the
Company's actual results to be materially different from any future
results, levels of activity, performance or achievements expressed
or implied by these forward-looking statements. You should not
place undue reliance on forward-looking statements since they
involve known and unknown risks, uncertainties and other factors
which are, in some cases, beyond the Company's control and which
could, and likely will, materially affect actual results, levels of
activity, performance or achievements. Any forward-looking
statement reflects the Company's current views with respect to
future events and is subject to these and other risks,
uncertainties and assumptions relating to the Company's operations,
results of operations, growth strategy and liquidity. More detailed
information about the Company and the risk factors that may affect
the realization of forward-looking statements is set forth in the
Company's most recent Annual Report on Form 10-K and other filings
with the Securities and Exchange Commission. Investors and security
holders are urged to read these documents free of charge on the
SEC's website at http://www.sec.gov. Except as may be required
by applicable law, The Company assumes no obligation to publicly
update or revise these forward-looking statements for any reason,
or to update the reasons actual results could differ materially
from those anticipated in these forward-looking statements, whether
as a result of new information, future events or otherwise.
1
|
Nierenberg et al.
International Journal of Bipolar Disorders (2023) 11:28
https://doi.org/10.1186/s40345-023-00
|
2
|
Grunebaum, et. al.,
Ketamine for Rapid Reduction of Suicidal Thoughts. Am J Psychiatry.
2018 Apr 1: 175(4): 327-335
|
3
|
Abbar, et. al. Ketamine
for Acute Treatment of Severe Suicidal Ideation, BMJ 2022;
376
|
4
|
https://www.cdc.gov/sepsis/what-is-sepsis.html
|
5
|
Open Forum Infectious
Diseases, Volume 9, Issue 7, July 2022, ofac315,
https://doi.org/10.1093/ofid/ofac315
|
View original content to download
multimedia:https://www.prnewswire.com/news-releases/nrx-pharmaceuticals-nasdaqnrxp-reports-first-quarter-2024-financial-results-and-provides-business-update-302145361.html
SOURCE NRx Pharmaceuticals, Inc.